The relationship between periosteal new bone formation and a number of infectious and metabolic conditions frequently seen in archeological human skeletal remains was investigated by studying human long bones demonstrating periosteal new bone formation archived in two London, UK, pathology museums: the St. George's Hospital Pathology Museum and the Hunterian Museum. The samples were subjected to macroscopic and radiographic analysis to determine if the characteristics of their periosteal lesions were specific to the corresponding disease states. The results demonstrated that no qualitative or quantitative characteristics of the periosteal reactions emerged that were specific to individual disease states. It was established that disease progression, rather than disease type, was the most important determinant of periosteal lesion appearance. A critical analysis of the bioarcheology literature pertaining to the recording and interpretation of periosteal reactions determined that the varied pathogenesis of periosteal new bone formation has been largely ignored in favor of a diagnosis of “nonspecific infection.” Assumptions regarding the infectious etiology of periosteal lesions have become embedded into the bioarcheology literature potentially skewing the results of skeletal population-based paleoepidemiological studies. Am J Phys Anthropol, 2008. © 2008 Wiley-Liss, Inc.